Lopinavir/ritonavir for treatment of non-hospitalized patients with COVID-19: a randomized clinical trial

DOI record: { "DOI": "10.1016/j.ijid.2022.12.028", "ISSN": [ "1201-9712" ], "URL": "http://dx.doi.org/10.1016/j.ijid.2022.12.028", "alternative-id": [ "S1201971222006658" ], "assertion": [ { "label": "This article is maintained by", "name": "publisher", "value": "Elsevier" }, { "label": "Article Title", "name": "articletitle", "value": "Lopinavir/ritonavir for treatment of non-hospitalized patients with COVID-19: a randomized clinical trial" }, { "label": "Journal Title", "name": "journaltitle", "value": "International Journal of Infectious Diseases" }, { "label": "CrossRef DOI link to publisher maintained version", "name": "articlelink", "value": "https://doi.org/10.1016/j.ijid.2022.12.028" }, { "label": "Content Type", "name": "content_type", "value": "article" }, { "label": "Copyright", "name": "copyright", "value": "© 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases." } ], "author": [ { "ORCID": "https://orcid.org/0000-0003-2334-5514", "affiliation": [], "authenticated-orcid": false, "family": "Kaizer", "given": "Alexander M.", "sequence": "first" }, { "affiliation": [], "family": "Shapiro", "given": "Nathan I.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-2927-8239", "affiliation": [], "authenticated-orcid": false, "family": "Wild", "given": "Jessica", "sequence": "additional" }, { "affiliation": [], "family": "Brown", "given": "Samuel M.", "sequence": "additional" }, { "affiliation": [], "family": "Cwik", "given": "B. Jessica", "sequence": "additional" }, { "affiliation": [], "family": "Hart", "given": "Kimberly W.", "sequence": "additional" }, { "affiliation": [], "family": "Jones", "given": "Alan E.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-5809-4060", "affiliation": [], "authenticated-orcid": false, "family": "Pulia", "given": "Michael S.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-9300-3045", "affiliation": [], "authenticated-orcid": false, "family": "Self", "given": "Wesley H.", "sequence": "additional" }, { "affiliation": [], "family": "Smith", "given": "Clay", "sequence": "additional" }, { "affiliation": [], "family": "Smith", "given": "Stephanie A.", "sequence": "additional" }, { "affiliation": [], "family": "Ng", "given": "Patrick C.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-6391-0448", "affiliation": [], "authenticated-orcid": false, "family": "Thompson", "given": "B. Taylor", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-7136-5408", "affiliation": [], "authenticated-orcid": false, "family": "Rice", "given": "Todd W.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-3297-2811", "affiliation": [], "authenticated-orcid": false, "family": "Lindsell", "given": "Christopher J.", "sequence": "additional" }, { "affiliation": [], "family": "Ginde", "given": "Adit A.", "sequence": "additional" } ], "container-title": "International Journal of Infectious Diseases", "container-title-short": "International Journal of Infectious Diseases", "content-domain": { "crossmark-restriction": true, "domain": [ "clinicalkey.fr", "clinicalkey.jp", "clinicalkey.es", "clinicalkey.com.au", "clinicalkey.com", "ijidonline.com", "elsevier.com", "sciencedirect.com" ] }, "created": { "date-parts": [ [ 2022, 12, 27 ] ], "date-time": "2022-12-27T00:44:50Z", "timestamp": 1672101890000 }, "deposited": { "date-parts": [ [ 2024, 5, 11 ] ], "date-time": "2024-05-11T14:46:17Z", "timestamp": 1715438777000 }, "indexed": { "date-parts": [ [ 2025, 5, 29 ] ], "date-time": "2025-05-29T18:23:23Z", "timestamp": 1748543003537, "version": "3.40.5" }, "is-referenced-by-count": 16, "issued": { "date-parts": [ [ 2023, 3 ] ] }, "language": "en", "license": [ { "URL": "https://www.elsevier.com/tdm/userlicense/1.0/", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 3, 1 ] ], "date-time": "2023-03-01T00:00:00Z", "timestamp": 1677628800000 } }, { "URL": "https://www.elsevier.com/legal/tdmrep-license", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 3, 1 ] ], "date-time": "2023-03-01T00:00:00Z", "timestamp": 1677628800000 } }, { "URL": "http://creativecommons.org/licenses/by-nc-nd/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 12, 21 ] ], "date-time": "2022-12-21T00:00:00Z", "timestamp": 1671580800000 } } ], "link": [ { "URL": "https://api.elsevier.com/content/article/PII:S1201971222006658?httpAccept=text/xml", "content-type": "text/xml", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://api.elsevier.com/content/article/PII:S1201971222006658?httpAccept=text/plain", "content-type": "text/plain", "content-version": "vor", "intended-application": "text-mining" } ], "member": "78", "original-title": [], "page": "223-229", "prefix": "10.1016", "published": { "date-parts": [ [ 2023, 3 ] ] }, "published-print": { "date-parts": [ [ 2023, 3 ] ] }, "publisher": "Elsevier BV", "reference": [ { "DOI": "10.1056/NEJMoa2007764", "article-title": "Remdesivir for the treatment of Covid-19 – Final Report", "author": "Beigel", "doi-asserted-by": "crossref", "first-page": "1813", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0001", "volume": "383", "year": "2020" }, { "DOI": "10.1056/NEJMoa2116846", "article-title": "Early remdesivir to prevent progression to severe Covid-19 in outpatients", "author": "Gottlieb", "doi-asserted-by": "crossref", "first-page": "305", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0002", "volume": "386", "year": "2022" }, { "DOI": "10.1001/jama.2021.0202", "article-title": "Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial", "author": "Gottlieb", "doi-asserted-by": "crossref", "first-page": "632", "journal-title": "JAMA", "key": "10.1016/j.ijid.2022.12.028_bib0003", "volume": "325", "year": "2021" }, { "DOI": "10.1056/NEJMoa2021436", "article-title": "Dexamethasone in hospitalized patients with Covid-19", "author": "Collaborative Group", "doi-asserted-by": "crossref", "first-page": "693", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0004", "volume": "384", "year": "2021" }, { "DOI": "10.1056/NEJMoa2031994", "article-title": "Baricitinib plus remdesivir for hospitalized adults with Covid-19", "author": "Kalil", "doi-asserted-by": "crossref", "first-page": "795", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0005", "volume": "384", "year": "2021" }, { "DOI": "10.1056/NEJMoa2035002", "article-title": "REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19", "author": "Weinreich", "doi-asserted-by": "crossref", "first-page": "238", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0006", "volume": "384", "year": "2021" }, { "DOI": "10.1016/j.antiviral.2022.105252", "article-title": "Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern", "author": "Vangeel", "doi-asserted-by": "crossref", "journal-title": "Antiviral Res", "key": "10.1016/j.ijid.2022.12.028_bib0007", "volume": "198", "year": "2022" }, { "DOI": "10.1056/NEJMc2201933", "article-title": "Efficacy of antiviral agents against the SARS-CoV-2 omicron subvariant BA.2", "author": "Takashita", "doi-asserted-by": "crossref", "first-page": "1475", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0008", "volume": "386", "year": "2022" }, { "DOI": "10.1016/S1473-3099(21)00751-9", "article-title": "Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial", "doi-asserted-by": "crossref", "first-page": "622", "journal-title": "Lancet Infect Dis", "key": "10.1016/j.ijid.2022.12.028_bib0009", "volume": "22", "year": "2022" }, { "article-title": "Molnupiravir and nirmatrelvir-ritonavir: oral Coronavirus Disease 2019 antiviral drugs", "author": "Saravolatz", "first-page": "ciac180", "journal-title": "Clin Infect Dis", "key": "10.1016/j.ijid.2022.12.028_bib0010", "year": "2022" }, { "DOI": "10.1111/bph.15819", "article-title": "How far are we from predicting multi-drug interactions during treatment for COVID-19 infection?", "author": "Lozano", "doi-asserted-by": "crossref", "first-page": "3831", "journal-title": "Br J Pharmacol", "key": "10.1016/j.ijid.2022.12.028_bib0011", "volume": "179", "year": "2022" }, { "DOI": "10.1038/s41467-022-29858-5", "article-title": "Comparing COVID-19-related hospitalization rates among individuals with infection-induced and vaccine-induced immunity in Israel", "author": "Waxman", "doi-asserted-by": "crossref", "first-page": "2202", "journal-title": "Nat Commun", "key": "10.1016/j.ijid.2022.12.028_bib0012", "volume": "13", "year": "2022" }, { "DOI": "10.1080/07853890.2022.2034936", "article-title": "Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19: a meta-analysis", "author": "Wen", "doi-asserted-by": "crossref", "first-page": "516", "journal-title": "Ann Med", "key": "10.1016/j.ijid.2022.12.028_bib0013", "volume": "54", "year": "2022" }, { "DOI": "10.15585/mmwr.mm7104e1", "article-title": "COVID-19 cases and hospitalizations by COVID-19 vaccination status and previous COVID-19 diagnosis—California and New York, May–November 2021", "author": "León", "doi-asserted-by": "crossref", "first-page": "125", "journal-title": "MMWR Morb Mortal Wkly Rep", "key": "10.1016/j.ijid.2022.12.028_bib0014", "volume": "71", "year": "2022" }, { "DOI": "10.7326/M21-4905", "article-title": "A longitudinal study of COVID-19 sequelae and immunity: baseline findings", "author": "Sneller", "doi-asserted-by": "crossref", "first-page": "969", "journal-title": "Ann Intern Med", "key": "10.1016/j.ijid.2022.12.028_bib0015", "volume": "175", "year": "2022" }, { "DOI": "10.7326/M22-1492", "article-title": "Understanding and improving recovery from COVID-19", "author": "Hope", "doi-asserted-by": "crossref", "first-page": "1041", "journal-title": "Ann Intern Med", "key": "10.1016/j.ijid.2022.12.028_bib0016", "volume": "175", "year": "2022" }, { "DOI": "10.1038/nrd.2015.37", "article-title": "Coronaviruses—drug discovery and therapeutic options", "author": "Zumla", "doi-asserted-by": "crossref", "first-page": "327", "journal-title": "Nat Rev Drug Discov", "key": "10.1016/j.ijid.2022.12.028_bib0017", "volume": "15", "year": "2016" }, { "DOI": "10.1093/infdis/jiv392", "article-title": "Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset", "author": "Chan", "doi-asserted-by": "crossref", "first-page": "1904", "journal-title": "J Infect Dis", "key": "10.1016/j.ijid.2022.12.028_bib0018", "volume": "212", "year": "2015" }, { "DOI": "10.1021/acs.jcim.0c00179", "article-title": "Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "3277", "journal-title": "J Chem Inf Model", "key": "10.1016/j.ijid.2022.12.028_bib0019", "volume": "60", "year": "2020" }, { "DOI": "10.1128/AAC.00399-20", "article-title": "Compounds with therapeutic potential against novel respiratory 2019 coronavirus", "author": "Martinez", "doi-asserted-by": "crossref", "journal-title": "Antimicrob Agents Chemother", "key": "10.1016/j.ijid.2022.12.028_bib0020", "volume": "64", "year": "2020" }, { "DOI": "10.3851/IMP3002", "article-title": "Combination therapy with lopinavir/ritonavir, ribavirin and interferon-α for Middle East respiratory syndrome", "author": "Kim", "doi-asserted-by": "crossref", "first-page": "455", "journal-title": "Antivir Ther", "key": "10.1016/j.ijid.2022.12.028_bib0021", "volume": "21", "year": "2016" }, { "DOI": "10.1016/j.bj.2020.11.005", "article-title": "Lopinavir/ritonavir: repurposing an old drug for HIV infection in COVID-19 treatment", "author": "Magro", "doi-asserted-by": "crossref", "first-page": "43", "journal-title": "Biomed J", "key": "10.1016/j.ijid.2022.12.028_bib0022", "volume": "44", "year": "2021" }, { "DOI": "10.1021/acs.biochem.0c00160", "article-title": "Why are lopinavir and ritonavir effective against the newly emerged coronavirus 2019? Atomistic insights into the inhibitory mechanisms", "author": "Nutho", "doi-asserted-by": "crossref", "first-page": "1769", "journal-title": "Biochemistry", "key": "10.1016/j.ijid.2022.12.028_bib0023", "volume": "59", "year": "2020" }, { "DOI": "10.1021/acs.jmedchem.5b01461", "article-title": "An overview of severe acute respiratory syndrome–coronavirus (SARS-CoV) 3CL protease inhibitors: peptidomimetics and small molecule chemotherapy", "author": "Pillaiyar", "doi-asserted-by": "crossref", "first-page": "6595", "journal-title": "J Med Chem", "key": "10.1016/j.ijid.2022.12.028_bib0024", "volume": "59", "year": "2016" }, { "DOI": "10.1056/NEJMoa2118542", "article-title": "Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19", "author": "Hammond", "doi-asserted-by": "crossref", "first-page": "1397", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0025", "volume": "386", "year": "2022" }, { "DOI": "10.1056/NEJMoa2001282", "article-title": "A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19", "author": "Cao", "doi-asserted-by": "crossref", "first-page": "1787", "journal-title": "N Engl J Med", "key": "10.1016/j.ijid.2022.12.028_bib0026", "volume": "382", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)32013-4", "article-title": "Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial", "doi-asserted-by": "crossref", "first-page": "1345", "journal-title": "Lancet", "key": "10.1016/j.ijid.2022.12.028_bib0027", "volume": "396", "year": "2020" }, { "article-title": "Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial", "author": "Li", "journal-title": "Med (N Y)", "key": "10.1016/j.ijid.2022.12.028_bib0028", "volume": "1", "year": "2020" }, { "DOI": "10.1001/jamanetworkopen.2021.6468", "article-title": "Effect of early treatment with hydroxychloroquine or lopinavir and ritonavir on risk of hospitalization among patients with COVID-19: the TOGETHER randomized clinical trial", "author": "Reis", "doi-asserted-by": "crossref", "journal-title": "JAMA Netw Open", "key": "10.1016/j.ijid.2022.12.028_bib0029", "volume": "4", "year": "2021" }, { "DOI": "10.1186/s13063-022-06213-z", "article-title": "Trial of Early antiviral Therapies during Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19: a summary of the protocol and analysis plan for a decentralized randomized controlled trial", "author": "Kaizer", "doi-asserted-by": "crossref", "first-page": "273", "journal-title": "Trials", "key": "10.1016/j.ijid.2022.12.028_bib0030", "volume": "23", "year": "2022" }, { "key": "10.1016/j.ijid.2022.12.028_bib0031", "unstructured": "World health organization. WHO R&D Blueprint: informal consultation on prioritization of candidate therapeutic agents for use in novel coronavirus 2019 infection, Geneva, Switzerland, 24 January 2020. Geneva: World Health Organization; 2020." }, { "key": "10.1016/j.ijid.2022.12.028_bib0032", "unstructured": "Harrell F. rmsb: Bayesian Regression Modeling Strategies. R package version 0.1.0 ed 2022. https://cran.r-project.org/web/packages/rmsb/index.html." }, { "DOI": "10.1093/jac/dkaa190", "article-title": "Lopinavir/ritonavir in COVID-19 patients: maybe yes, but at what dose?", "author": "Baldelli", "doi-asserted-by": "crossref", "first-page": "2704", "journal-title": "J Antimicrob Chemother", "key": "10.1016/j.ijid.2022.12.028_bib0033", "volume": "75", "year": "2020" }, { "DOI": "10.3389/fphar.2021.704767", "article-title": "High dose lopinavir/ritonavir does not lead to sufficient plasma levels to inhibit SARS-CoV-2 in hospitalized patients with COVID-19", "author": "Karolyi", "doi-asserted-by": "crossref", "journal-title": "Front Pharmacol", "key": "10.1016/j.ijid.2022.12.028_bib0034", "volume": "12", "year": "2021" }, { "DOI": "10.1128/AAC.01177-20", "article-title": "Effect of systemic inflammatory response to SARS-CoV-2 on lopinavir and hydroxychloroquine plasma concentrations", "author": "Marzolini", "doi-asserted-by": "crossref", "journal-title": "Antimicrob Agents Chemother", "key": "10.1016/j.ijid.2022.12.028_bib0035", "volume": "64", "year": "2020" } ], "reference-count": 35, "references-count": 35, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S1201971222006658" } }, "score": 1, "short-title": [], "source": "Crossref", "special_numbering": "C", "subject": [], "subtitle": [], "title": "Lopinavir/ritonavir for treatment of non-hospitalized patients with COVID-19: a randomized clinical trial", "type": "journal-article", "update-policy": "https://doi.org/10.1016/elsevier_cm_policy", "volume": "128" }